Evaluation of immune infiltrate according to the HER2 status in colorectal cancer.

Colorectal cancer HER2 Immune infiltrate QuPath software

Journal

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385

Informations de publication

Date de publication:
14 Oct 2023
Historique:
received: 01 04 2023
revised: 11 08 2023
accepted: 05 09 2023
medline: 17 10 2023
pubmed: 17 10 2023
entrez: 16 10 2023
Statut: aheadofprint

Résumé

In colorectal cancer (CRC), HER2 targeting is a promising treatment and immune infiltrate is an important area of research and strategy. Data regarding HER2 status and immune infiltrate are lacking. The aim of this study was to compare the immune infiltrate between HER2 amplified and non-amplified categories in proficient MisMatchRepair (pMMR)/microsatellite stable (MSS) CRC. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization were performed in a retrospective series of 654 CRC. Lymphocyte infiltrate was analysed by anti-CD3, CD8 and CD4 IHC and evaluated digitally using QuPath software. Among the 654 CRC, we first observed a decreased CD3+ and CD8+ infiltrate between HER2 amplified (all IHC 3+ except one 2+) and non-amplified HER2 2+ IHC CRC (p = 0.059 and 0.072 respectively). A supplementary analysis of 258 pMMR/MSS CRC from the previous cohort, displaying all the IHC scores (0, 1+, 2+, 3+), showed a lower CD3+ infiltrate between HER2 amplified versus HER2 0 (p = 0.002), 1+ (p = 0.088) and non-amplified 2+ (p = 0.081) IHC cases. Our original findings suggest that in pMMR/MSS CRC, the immune infiltrate is reduced in HER2 amplified versus other HER2 categories. These data might be useful for future strategies combining anti-HER2 treatments and immune checkpoint inhibitors and need to be confirmed in larger CRC cohorts.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
In colorectal cancer (CRC), HER2 targeting is a promising treatment and immune infiltrate is an important area of research and strategy. Data regarding HER2 status and immune infiltrate are lacking. The aim of this study was to compare the immune infiltrate between HER2 amplified and non-amplified categories in proficient MisMatchRepair (pMMR)/microsatellite stable (MSS) CRC.
METHODS METHODS
HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization were performed in a retrospective series of 654 CRC. Lymphocyte infiltrate was analysed by anti-CD3, CD8 and CD4 IHC and evaluated digitally using QuPath software.
RESULTS RESULTS
Among the 654 CRC, we first observed a decreased CD3+ and CD8+ infiltrate between HER2 amplified (all IHC 3+ except one 2+) and non-amplified HER2 2+ IHC CRC (p = 0.059 and 0.072 respectively). A supplementary analysis of 258 pMMR/MSS CRC from the previous cohort, displaying all the IHC scores (0, 1+, 2+, 3+), showed a lower CD3+ infiltrate between HER2 amplified versus HER2 0 (p = 0.002), 1+ (p = 0.088) and non-amplified 2+ (p = 0.081) IHC cases.
CONCLUSIONS CONCLUSIONS
Our original findings suggest that in pMMR/MSS CRC, the immune infiltrate is reduced in HER2 amplified versus other HER2 categories. These data might be useful for future strategies combining anti-HER2 treatments and immune checkpoint inhibitors and need to be confirmed in larger CRC cohorts.

Identifiants

pubmed: 37845155
pii: S1590-8658(23)00959-3
doi: 10.1016/j.dld.2023.09.015
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of Interest Chloé Molimard, Fanny Dor, Alexis Overs, Franck Monnien, Grégoire Gessain, Loïs Kedochim, Flavia D'Angelo, Marine Abad, Morgane Heberle, Valentin Derangère, François Ghiringhelli, Lucine Vuitton, Séverine Valmary-Degano, Christophe Borg, Zaher Lakkis, Frédéric Bibeau have no competing financial interests of personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Chloé Molimard (C)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France. Electronic address: cmolimard@chu-besancon.fr.

Fanny Dor (F)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France.

Alexis Overs (A)

Department of Oncobiology, University Hospital of Besançon, Besançon, France.

Franck Monnien (F)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France.

Grégoire Gessain (G)

University of Paris, Health Faculty, Paris, France.

Loïs Kedochim (L)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France.

Flavia D'Angelo (F)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France.

Marine Abad (M)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France.

Morgane Heberle (M)

Department of Clinical Research, University Hospital of Besançon, Besançon, France.

Valentin Derangère (V)

Cancer Biology Transfer Platform, Centre Georges-François Leclerc, F-21000 Dijon, France.

François Ghiringhelli (F)

Department of Medical Oncology, Centre Georges-François Leclerc, F-21000 Dijon, France.

Lucine Vuitton (L)

Department of Gastroenterology, University Hospital of Besançon, Besançon, France.

Séverine Valmary-Degano (S)

University Grenoble Alpes, Inserm U1209, CNRS UMR5309, Institute for Advanced Biosciences, CHU de Grenoble-Alpes, F-38000 Grenoble, France.

Christophe Borg (C)

Department of Oncology, University Hospital of Besançon, Besançon, France.

Zaher Lakkis (Z)

Department of Digestive Surgery, University Hospital of Besançon, Besançon, France.

Fréderic Bibeau (F)

Department of Pathology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, 25000 Besançon, France.

Classifications MeSH